Proper regulation of the growth and death of individual cells is fundamental for the development and normal function of complex organisms. An understanding of cell growth control is emerging from genetic, molecular and biochemical studies in many organisms that have lead to a detailed mechanistic description of the cell cycle and its regulation. The realization that, similar to cell growth, cell death is an orderly process that is critical for organogenesis, and that abnormal regulation of cell death can be a critical initiating event in human disease, has stimulated a great deal of interest in discovering its mechanistic basis. Genetic studies of the stereotyped death of individual cells during development of C. elegans have led to identification of several genes that are regulators of programmed cell death, and have provided a gross outline for the cell death pathway. Convincing evidence that some of these molecules are fundamental participants in the cell death pathway in all metazoans has emerged from parallel studies of mammalian genes first identified in the context of oncogenesis and later shown to allow abnormal cell expansion due to failures in programmed cell death. For example, the C. elegans ced 9 gene and the mammalian bcl-2 gene are demonstrated functional homologues that can prevent programmed death in both insect and mammalian cells. The mammalian ICE like proteases and C. elegans ced 3 genes are also functionally homologous, although in this case their role is to induce apoptotic death. While definition of the specific mechanisms through which these molecules act is an area of intense investigation, an appreciation that the program mediating cell death may be as complex as that regulating cell growth is also emerging.
In the absence of testosterone, programmed cell death is triggered in the prostate and the prostate dies. Therefore, a castrated mammal may be used as an experimental animal model for programmed cell death. During this process, certain detrimental genes will presumably be turned on, and certain genes necessary for a normal, healthy prostate will presumably be turned off. Such an experimental animal model may be used to study mechanisms related to programmed cell death, most notably cancer.
Recent studies indicate that all human males will eventually develop prostate cancer, if they live long enough. For example, 50% of all men over 50 and essentially all men over 70 suffer from some form of prostate hyperplasia. Annually, 250,000 new cases of prostate cancer are diagnosed, and despite the $4 billion dollars spent to treat this ailment, 40,000 men die of prostate cancer each year. As the United States population continues to age, due to the aging of the post-World War II baby boomers, these numbers can only be expected to rise.
One particular aspect of prostate cancer is that it oftentimes strikes relatively late in life and then progresses slowly. Thus, for many older men, the best treatment would be to simply monitor the progression of the cancer rather than aggressively attack it, since under such circumstances it is far more likely that the patient will succumb to other causes of death, long before the prostate cancer becomes life-threatening. Unfortunately, there presently exists a definite lack of a means for accurately monitoring and more importantly, accurately predicting the progression of prostate cancer. Current technology relies on monitoring the protein PSA, which can result in a high percentage of false positives, and cannot be used as a predictor of the future progression of the disease. Therefore, there is a need to identify means of obtaining other factors that could be diagnostic of prostate cancer. Furthermore, there is a need to identify means that can be used to predict the future progression of prostate hyperplasia. Finally, there is a need to identify means that can be used to identify stages of prostate regression.
The citation of any reference herein should not be construed as an admission that such reference is available as "Prior Art" to the instant application.